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Licensed Unlicensed Requires Authentication Published by De Gruyter February 14, 2020

Influence of pancreatic status on circulating plasma sterols in patients with cystic fibrosis

  • Monica Gelzo , Paola Iacotucci , Concetta Sica , Renato Liguori , Marika Comegna , Vincenzo Carnovale , Antonio Dello Russo , Gaetano Corso EMAIL logo and Giuseppe Castaldo



Patients with cystic fibrosis (CF) have a reduced intestinal absorption of cholesterol and in a preliminary study we observed differences in plasma sterol profile between patients with pancreatic sufficiency (PS) and those with pancreatic insufficiency (PI). Therefore, we hypothesized that the sterol analysis may contribute to study the digestion and absorption state of lipids in patients with CF. To this aim we evaluated plasma sterols in a significant number of adult patients with CF in relation to the pancreatic status.


Beside cholesterol, we measured phytosterols and lathosterol as markers of intestinal absorption and hepatic biosynthesis, respectively, by gas-chromatography in plasma of adult CF patients with pancreatic sufficiency (PS-CF, n = 57), insufficiency (PI-CF, n = 97) and healthy subjects (control group, CT, n = 71).


PI-CF patients had cholesterol and phytosterols levels significantly lower than PS-CF and CT (p < 5 × 10−10) suggesting a reduced intestinal absorption of sterols related to PI. Instead, lathosterol was significantly higher in PI-CF patients than PS-CF and CT (p < 0.0003) indicating an enhanced cholesterol biosynthesis. In PI-CF patients, phytosterols positively correlate with vitamin E (p = 0.004). Both the classes of molecules need cholesterol esterase for the intestinal digestion, thus the reduced levels of such lipids in serum from PI-CF patients may depend on a reduced enzyme activity, despite the pancreatic enzyme supplementation in all PI-CF patients.


A plasma sterols profile may be useful to evaluate the metabolic status of lipids in adult patients with CF and could help to manage the pancreatic enzyme supplementation therapy.

Funding source: Regione Campania

Award Identifier / Grant number: Quota vincolata per la prevenzione e cura della Fi

Funding statement: Funder Name: Regione Campania, Funder Id:, Grant Number: Quota vincolata per la prevenzione e cura della Fi.


Grants from Ministero della Salute (Rome, Italy) L.548/93 and Campania Region (regional research funding quote of years 2013–15) are gratefully acknowledged.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Employment or leadership: None declared.

  3. Honorarium: None declared.

  4. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


1. Cantin AM, Hartl D, Konstan MW, Chmiel JF. Inflammation in cystic fibrosis lung disease: pathogenesis and therapy. J Cyst Fibros 2015;14:419–30.10.1016/j.jcf.2015.03.003Search in Google Scholar PubMed

2. Terlizzi V, Lucarelli M, Salvatore D, Angioni A, Bisogno A, Braggion C, et al. Clinical expression of cystic fibrosis in a large cohort of Italian siblings. BMC Pulm Med 2018;18:196.10.1186/s12890-018-0766-6Search in Google Scholar PubMed PubMed Central

3. Ledder O, Haller W, Couper RT, Lewindon P, Oliver M. Cystic fibrosis: an update for clinicians. Part 2: hepatobiliary and pancreatic manifestations. J Gastroenterol Hepatol 2014;29:1954–62.10.1111/jgh.12785Search in Google Scholar PubMed

4. Gibson-Corley KN, Meyerholz DK, Engelhardt JF. Pancreatic pathophysiology in cystic fibrosis. J Pathol 2016;238:311–20.10.1002/path.4634Search in Google Scholar PubMed PubMed Central

5. Peretti N, Marcil V, Drouin E, Levy E. Mechanisms of lipid malabsorption in cystic fibrosis: the impact of essential fatty acids deficiency. Nutr Metab 2005;2:11.10.1186/1743-7075-2-11Search in Google Scholar PubMed PubMed Central

6. Turck D, Braegger CP, Colombo C, Declercq D, Morton A, Pancheva R, et al. ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clin Nutr 2016;35:557–77.10.1016/j.clnu.2016.03.004Search in Google Scholar PubMed

7. Ianiro G, Pecere S, Giorgio V, Gasbarrini A, Cammarota G. Digestive enzyme supplementation in gastrointestinal diseases. Curr Drug Metab 2016;17:187–93.10.2174/138920021702160114150137Search in Google Scholar PubMed PubMed Central

8. Drzymała-Czyż S, Jończyk-Potoczna K, Lisowska A, Stajgis M, Walkowiak J. Supplementation of ursodeoxycholic acid improves fat digestion and absorption in cystic fibrosis patients with mild liver involvement. Eur J Gastroenterol Hepatol 2016;28:645–9.10.1097/MEG.0000000000000593Search in Google Scholar PubMed

9. Elce A, Nigro E, Gelzo M, Iacotucci P, Carnovale V, Liguori R, et al. Supervised physical exercise improves clinical, anthropometric and biochemical parameters in adult cystic fibrosis patients: a 2-year evaluation. Clin Respir J 2018;12:2228–34.10.1111/crj.12796Search in Google Scholar PubMed

10. Panagopoulou P, Fotoulaki M, Nikolaou A, Nousia-Arvanitakis S. Prevalence of malnutrition and obesity among cystic fibrosis patients. Pediatr Int 2014;56:89–94.10.1111/ped.12214Search in Google Scholar PubMed

11. Figueroa V, Milla C, Parks EJ, Schwarzenberg SJ, Moran A. Abnormal lipid concentrations in cystic fibrosis. Am J Clin Nutr 2002;75:1005–11.10.1093/ajcn/75.6.1005Search in Google Scholar PubMed

12. Taylor CJ, Chen K, Horvath K, Hughes D, Lowe ME, Mehta D, et al. ESPGHAN and NASPGHAN report on the assessment of exocrine pancreatic function and pancreatitis in Children. J Pediatr Gastroenterol Nutr 2015;61:144–53.10.1097/MPG.0000000000000830Search in Google Scholar PubMed

13. Gelzo M, Sica C, Elce A, Dello Russo A, Iacotucci P, Carnovale V, et al. Reduced absorption and enhanced synthesis of cholesterol in patients with cystic fibrosis: a preliminary study of plasma sterols. Clin Chem Lab Med 2016;54:1461–6.10.1515/cclm-2015-1151Search in Google Scholar PubMed

14. Farrell PM, White TB, Ren CL, Hempstead SE, Accurso F, Derichs N, et al. Diagnosis of cystic fibrosis: consensus guidelines from the cystic fibrosis foundation. J Pediatr 2017;181 Suppl:4–15.10.1016/j.jpeds.2016.09.064Search in Google Scholar PubMed

15. Castellani C, Duff AJ, Bell SC, Heijerman HG, Munck A, Ratjen F, et al. ECFS best practice guidelines: the 2018 revision. J Cyst Fibros 2018;17:153–78.10.1016/j.jcf.2018.02.006Search in Google Scholar PubMed

16. Tomaiuolo R, Sangiuolo F, Bombieri C, Bonizzato A, Cardillo G, Raia V, et al. Epidemiology and a novel procedure for large scale analysis of CFTR rearrangements in classic and atypical CF patients: a multicentric Italian study. J Cyst Fibrosis 2008;7:347–51.10.1016/j.jcf.2007.12.004Search in Google Scholar PubMed

17. Amato F, Bellia C, Cardillo G, Castaldo G, Ciaccio M, Elce A, et al. Extensive molecular analysis of patients bearing CFTR-related disorders. J Mol Diagn 2012;14:81–9.10.1016/j.jmoldx.2011.09.001Search in Google Scholar PubMed

18. Corso G, Gelzo M, Barone R, Clericuzio S, Pianese P, Nappi A, et al. Sterol profiles in plasma and erythrocyte membranes in patients with Smith-Lemli-Opitz syndrome: a six-year experience. Clin Chem Lab Med 2011;49:2039–46.10.1515/CCLM.2011.689Search in Google Scholar PubMed

19. Hammer Ø, Harper DA, Ryan PD. PAST: paleontological statistics software package for education and data analysis. Palaeontol Electron 2001;1:9.Search in Google Scholar

20. Howles PN, Hui DY. Chapter 7. Cholesterol Esterase. In: Mansbach II CM, Tso P, Kuksis A, editors. Intestinal lipid metabolism. New York: Springer Science & Business Media, 2001:119–34.10.1007/978-1-4615-1195-3_7Search in Google Scholar

21. Moreau RA, Hicks KB. The in vitro hydrolysis of phytosterol conjugates in food matrices by mammalian digestive enzymes. Lipids 2004;39:769–76.10.1007/s11745-004-1294-3Search in Google Scholar PubMed

22. Lombardo D, Guy O. Studies on the substrate specificity of a carboxyl ester hydrolase from human pancreatic juice. II. Action on cholesterol esters and lipid-soluble vitamin esters. Biochim Biophys Acta 1980;611:147–55.10.1016/0005-2744(80)90050-9Search in Google Scholar

23. Walters MP, Conway SP. Cholesterol esterase activities in commercial pancreatic enzyme preparations and implications for use in pancreatic insufficient cystic fibrosis. J Clin Pharm Ther 2001;26:425–31.10.1046/j.1365-2710.2001.00379.xSearch in Google Scholar PubMed

24. Zhang Z, Pereira SL, Luo M, Matheson EM. Evaluation of blood biomarkers associated with risk of malnutrition in older adults: a systematic review and meta-analysis. Nutrients 2017;9:829.10.3390/nu9080829Search in Google Scholar PubMed PubMed Central

25. Fang D, West RH, Manson ME, Ruddy J, Jiang D, Previs SF, et al. Increased plasma membrane cholesterol in cystic fibrosis cells correlates with CFTR genotype and depends on de novo cholesterol synthesis. Respir Res 2010;11:61.10.1186/1465-9921-11-61Search in Google Scholar PubMed PubMed Central

26. Elmehdawi RR. Hypolipidemia: a word of caution. Libyan J Med 2008;3:84–90.10.3402/ljm.v3i2.4764Search in Google Scholar

Received: 2019-10-28
Accepted: 2019-12-26
Published Online: 2020-02-14
Published in Print: 2020-09-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

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